This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatitis C virus infections affect approximately 2% of the worldwide population. The virus has a high propensity for inducing persistent infection that over time progress to serious liver disease including cirrhosis and liver cancer. Research on HCV has been impeded by the lack of a small animal model and a tissue culture system. GBV-B is the virus phylogenetically most closely related to HCV and it causes hepatitis in tamarins. We have developed the GBV-B animal model as a surrogate small primate model for HCV. We have recently demonstrated that the common marmoset is equally permissive for GBV-B infections and is now the preferred animal model. In addition, we have developed a robust tissue culture system for GBV-B utilizing primary hepatocyte cultures from tamarins or marmosets. In this proposal, we will more fully develop the animal and culture models for GBV-B and test specific hypotheses relevant to HCV disease.